PF-8380 and closely related analogs: synthesis and structure-activity relationship towards autotaxin inhibition and glioma cell viability

Arch Pharm (Weinheim). 2013 Feb;346(2):91-7. doi: 10.1002/ardp.201200395. Epub 2013 Jan 8.

Abstract

A series of PF-8380 analogs, a recently developed autotaxin inhibitor, was explored. Inhibition of autotaxin by these analogs, as well as by all PF-8380 synthetic intermediates, shows the importance of meta-dichlorobenzyl and benzo[d]oxazol-2(3H)-one fragments. However, analogs 8 and 9, bearing only the benzo[d]oxazol-2(3H)-one moiety, are more cytotoxic on the LN229 glioblastoma cell line than PF-8380 and temozolomide (TMZ).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Benzoxazoles* / chemical synthesis
  • Benzoxazoles* / chemistry
  • Benzoxazoles* / pharmacology
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Design
  • Glioblastoma / enzymology
  • Glioblastoma / pathology
  • Humans
  • Molecular Structure
  • Phosphodiesterase Inhibitors* / chemical synthesis
  • Phosphodiesterase Inhibitors* / chemistry
  • Phosphodiesterase Inhibitors* / pharmacology
  • Phosphoric Diester Hydrolases / metabolism*
  • Piperazines* / chemical synthesis
  • Piperazines* / chemistry
  • Piperazines* / pharmacology
  • Structure-Activity Relationship

Substances

  • 6-(3-(piperazin-1-yl)propanoyl)benzo(d)oxazol-2(3H)-one
  • Antineoplastic Agents
  • Benzoxazoles
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Phosphoric Diester Hydrolases
  • alkylglycerophosphoethanolamine phosphodiesterase